Idiotypic regulation of the immune system by the induction of antibodies against anti-idiotypic antibodies.

Abstract

Anticarbohydrate antibodies (Abl) were isolated from a rabbit hyperimmunized with Micrococcus lysodeikticus and injected into allotype-matched rabbits in order to obtain specific anti-iodiotypic antibodies (Ab2). Ab2 was isolated by means of a Sepharose column coupled to the anticarbohydrate antibodies and was injected into two allotypematched rabbits. These latter rabbits produced specific antianti-idiotypic antibodies (Ab3) probably sharing idiotypic specificities with Abl. However, these Ab3 did not react with the antigenic carbohydrate moiety of bacteria. The two rabbits that had produced Ab3 were then immunized with M. lysodeikticus and synthesized anticarbohydrate antibodies (Abl') bearing idiotypic specificities similar to those of Abl. The immune repertoire which is effectively expressed in one individual depends not only on the antigenic stimulation but also on the previous idiotypic history of the individual. These data support the concept that the immune system is a functional idiotypic network.As a rule, in response to the same antigen, different individuals from the same species express different subsets of the total antibody repertoire of the species, with each subset bearing different idiotypic specificities (1-7) (these antibodies will be referred to as Abl). Idiotypic similarities were observed only in certain idiotypic systems (5,8) and were only partial with two main kinds of exceptions: (i) some rabbit families or some inbred strains of mice immunized with certain antigens synthesize antibodies with very similar idiotypic specificities (9-11); and (ii) very similar idiotypic specificities are often found among different antibody subpopulations present in the serum of a single individual immunized with a single antigen (12)(13)(14)(15)(16)(17)(18)(19)(20).The V domains of anti-idiotypic antibodies (which will be called Ab2) might themselves function as antigens and therefore elicit the synthesis of anti-anti-idiotypic antibodies (which will be referred to as AbS). These AbS might elicit the synthesis of Ab4, and so on. If Sepharose (21). The main fraction of anti-CHO antibodies from rabbit 2975 was eluted from the immunoadsorbent with 5% glucose in phosphate-buffered 0.15 M NaCl (Pi/NaCl), pH 7.5. Ab2 anti-idiotypic antisera were raised in allotype-matched rabbits.Allotypes tested were al, a2, a3, b4, b5, b6, b9, c7, c21, e14, dlI, and d12. Purified anti-CHO antibodies from rabbit 2975 (Abl) were polymerized with glutaraldehyde as described (22) and injected into six allotype-matched rabbits. Injections of 1 mg of AbI emulsified in complete Freund's adjuvant twice a week during 1 month was followed by the injection of 1 mg of AbI intravenously. Abl (1 mg) in incomplete Freund's adjuvant was then injected once a week. Ab2 from rabbit II (2238) were purified by means of a Sepharose column to which 200 mg of Ab had been coupled. Twenty milliliters of serum 2238 (Ab2) was passed through the column. After extensive washing, bound proteins were eluted with glycine-HCI, pH 2.2, and their i...

Suppression of in vitro monoclonal human rheumatoid factor synthesis by antiidiotypic antibody. Target cells and molecular requirements.

“…In the latter case, both in vitro and in vivo studies have demonstrated that antiidiotypic antibody is capable of modulating subsequent expression of idiotype. The seemingly paradoxical capacity of antiidiotypic antibody to either induce (9)(10)(11)(12)(13)(14)(15) or suppress (5-8) expression of idiotype is consistent with other observations that interactions between idiotype and antiidiotype are demonstrable in both helper (3) and suppressor (2) regulatory T cell circuits. Despite evidence that antiidiotypic antibody is capable of potently regulating levels of idiotype, mechanisms underlying the effects of antiidiotypic antibody remain unclear.…”

Analyses of Idiotypes on Anti‐α‐1, 6‐Dextran Antibodies in Mice

“…Recently, an important role of the Id/anti-Id network in regulation of immune responses has been elucidated (3,12,17,28). The fact that a pauciclonal and very intense response to dextran TlO-KLH was observed with strict consistency in all individual mice of the C57BL/6 strain should be useful for studies on the role of the Id/anti-Id network in immune responses.…”

Enhancement of antibody response by mouse dendritic cells pulsed with tobacco mosaic virus or with rabbit antiidiotypic antibodies raised against a private rabbit idiotype.

“…It has been shown, first in rabbits (1,2) and then in mice (3)(4)(5)(6), that silent idiotypes (Id) can be induced at will by using the idiotypic cascade. However, in most, but not all, of these experiments large amounts of antiidiotypic antibodies (Ab2) as well as nonphysiological adjuvants such as polyclonal activators were used (7).…”